Kirkwood Zara I, Millar Beverley C, Downey Damian G, Moore John E
Centre for Experimental Medicine, Queen's University; Department of Bacteriology, Northern Ireland Public Health Laboratory, Belfast City Hospital, Northern Ireland, UK.
Centre for Experimental Medicine, Queen's University, Northern Ireland, UK.
Int J Mycobacteriol. 2018 Oct-Dec;7(4):358-360. doi: 10.4103/ijmy.ijmy_142_18.
Antimicrobial resistance (AMR) has rendered certain species of Mycobacterium difficult to treat clinically, particularly the nontuberculous Mycobacterium, Mycobacterium abscessus, in patients with cystic fibrosis (CF). Such patients are treated with several nonantibiotic medicines, which may have antimicrobial properties. Given the growing burden of AMR in M. abscessus, it is importtant to investigate the antimicrobial activity of all medicines used in the treatment of such patients. It was, therefore, the aim of this study to examine the antimicrobial activity of 10 nonantibiotic medicines used commonly in the treatment of CF.
Antibiotic susceptibility studies were performed on human clinical isolates of M. abscessus (n = 16) including 11 smooth isolates, four rough isolates and one Reference isolate (NCTC 13031), against the following 10 nonantibiotic medicines:-aspirin (850 ug/ml), chlorphenamine (400 ug/ml), Creon (4000 international units/ml), cyclizine (50 mg/ml), DNase (1 μg/ml), hypertonic saline (NaCl) 7% (w/v), ibuprofen (44.4 mg/ml), lansoprazole (300 ug/ml), paracetamol (10 mg/ml), and prednisolone (500 ug/ml).
Of the 10 nonantibiotic drugs investigated, inhibition of M. abscessus was noted with chlorphenamine (400 ug/ml), cyclizine (50 mg/ml), ibuprofen (44.4 mg/ml) and lansoprazole (300 ug/ml), with no activity associated with aspirin (850 ug/ml), Creon (4000 international units/ml), DNase (1 μg/ml), hypertonic saline (NaCl) 7% (w/v), paracetamol (10 mg/ml), and prednisolone (500 ug/ml). The minimum inhibitory concentration (MIC) of cyclizine to M. abscessus (n = 6) ranged from 8.0 to 12.5 ug/ml, with a mean MIC, MIC, and MICof 10.6, 10.0 and 12.5 ug/ml, respectively.
This study identified that chlorphenamine, cyclizine, ibuprofen, and lansoprazole have in vitro antimycobacterial activity against clinical M. abscessus, isolated from patients with CF. Further studies should now examine potential antimicrobial synergy between these compounds and common conventional antimycobacterial antibiotics, including the macrolides and fluoroquinolones, to decide how best to exploit such positive interactions to reduce AMR burden and improve treatment regimens.
抗生素耐药性（AMR）已使某些分枝杆菌在临床上难以治疗，尤其是囊性纤维化（CF）患者中的非结核分枝杆菌脓肿分枝杆菌。此类患者使用几种可能具有抗菌特性的非抗生素药物进行治疗。鉴于脓肿分枝杆菌中AMR的负担日益加重，研究用于治疗此类患者的所有药物的抗菌活性非常重要。因此，本研究的目的是检测常用于治疗CF的10种非抗生素药物的抗菌活性。
对脓肿分枝杆菌的人类临床分离株（n = 16）进行抗生素敏感性研究，其中包括11株光滑型分离株、4株粗糙型分离株和1株参考分离株（NCTC 13031），针对以下10种非抗生素药物：阿司匹林（850微克/毫升）、氯苯那敏（400微克/毫升）、胰酶肠溶胶囊（4000国际单位/毫升）、赛克利嗪（50毫克/毫升）、脱氧核糖核酸酶（1微克/毫升）、7%（w/v）高渗盐水（氯化钠）、布洛芬（44.4毫克/毫升）、兰索拉唑（300微克/毫升）、对乙酰氨基酚（10毫克/毫升）和泼尼松龙（500微克/毫升）。
在所研究的10种非抗生素药物中，氯苯那敏（400微克/毫升）、赛克利嗪（50毫克/毫升）、布洛芬（44.4毫克/毫升）和兰索拉唑（300微克/毫升）对脓肿分枝杆菌有抑制作用，而阿司匹林（850微克/毫升）、胰酶肠溶胶囊（4000国际单位/毫升）、脱氧核糖核酸酶（1微克/毫升）、7%（w/v）高渗盐水（氯化钠）、对乙酰氨基酚（10毫克/毫升）和泼尼松龙（500微克/毫升）无活性。赛克利嗪对脓肿分枝杆菌（n = 6）的最低抑菌浓度（MIC）范围为8.0至12.5微克/毫升，平均MIC、MIC和MIC分别为10.6微克/毫升、10.0微克/毫升和12.5微克/毫升。
本研究确定氯苯那敏、赛克利嗪、布洛芬和兰索拉唑对从CF患者中分离出的临床脓肿分枝杆菌具有体外抗分枝杆菌活性。现在应进一步研究这些化合物与常见的传统抗分枝杆菌抗生素（包括大环内酯类和氟喹诺酮类）之间潜在的抗菌协同作用，以确定如何最好地利用这种积极相互作用来减轻AMR负担并改善治疗方案。
